ADIPOQ gene polymorphisms and haplotypes linked to altered susceptibility to PCOS: a case-control study.

Research Question: What role do ADIPOQ variants play in controlling adiponectin concentrations and altered risk of polycystic ovary syndrome (PCOS)?

Design: Study subjects comprised 583 women with PCOS and 713 age-matched controls. Genotyping of rs182052, rs822393, rs822396, rs7649121, rs3774271, rs266729, rs3774261 and rs6773957 ADIPOQ polymorphisms was done by real-time polymerase chain reaction (PCR).

Results: Of the 16 ADIPOQ variants, the minor allele frequencies of rs182052, rs822393, rs822396, rs7649121, rs3774261 and rs6773957 were significantly different between PCOS cases and controls. Significant differences in rs266729 (P = 0.02), rs822396 (P = 0.02), rs3774261 (P < 0.001) and rs6773957 (P < 0.001) genotypes were also noted between PCOS cases and controls. Reduced PCOS risk was found with heterozygous rs266729, while increased risk was linked to heterozygous rs822396 and homozygous minor allele rs3774361, and in heterozygous and homozygous minor allele rs6773957 genotype carriers. Haplotype analysis identified two blocks based on linkage disequilibrium pattern; alleles coded as '1' (major) and '2' (minor). Within Block 1 (rs4632532, rs16861194, rs266729, rs182052, rs16861209, rs822393, rs822395, rs822396, rs7649121), haplotypes 111111111 and 212211221 were positively, while haplotypes 212212112 and 212211211 were negatively associated with PCOS. Within Block 2 (rs2241766, rs1501299, rs2241767, rs3774261, rs6773957, rs1063539) haplotypes 111221 and 112221 were positively, while haplotype 111111 was negatively associated with PCOS.

Conclusions: This is the first study to confirm the association of rs182052, rs822393, rs7649121 and rs6773957 ADIPOQ variants with altered risk of PCOS. The varied association of ADIPOQ variants with PCOS in relation to earlier reports indicate there is an ethnic contribution to ADIPOQ association with PCOS.